Osteopontin deletion drives hematopoietic stem cell mobilization to the liver and increases hepatic iron contributing to alcoholic liver disease.
Osteopontin deletion drives hematopoietic stem cell mobilization to the liver and increases hepatic iron contributing to alcoholic liver disease.
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骨桥蛋白缺失将造血干细胞动员驱动向肝脏动员，并增加对酒精性肝病的肝铁。
DOI：
10.1002/hep4.1116
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发表时间：
2018-01
影响因子：
5.1
通讯作者：
Nieto N
中科院分区：
文献类型：
--
作者：
Magdaleno F;Ge X;Fey H;Lu Y;Gaskell H;Blajszczak CC;Aloman C;Fiel MI;Nieto N
本研究旨在探讨骨桥蛋白（OPN）在造血干细胞（HPSC）向肝脏动员中的作用及其在酒精性肝病（ALD）中的作用。我们分析了年轻（14 - 16周）和老年（>1.5岁）野生型（WT）同窝仔和全局Opn敲除（Opn−/−）小鼠的HPSC动员到肝脏。此外，WT和Opn−/−小鼠长期喂食Lieber-DeCarli饮食7周。通过流式细胞术分析骨髓（BM）、血液、脾脏和肝脏中的HPSC祖细胞和多形核中性粒细胞（PMN）。测定血清和肝脏中的趋化因子、生长因子和细胞因子。在肝脏切片上进行普鲁士蓝染色用于铁沉积物和萘酚AS-D氯乙酸酯酶染色用于PMN。与老年Opn−/−小鼠相比，年轻小鼠的肝脏和BM中的造血祖细胞较低。粒细胞集落刺激因子和巨噬细胞集落刺激因子在Opn−/−小鼠中增加，表明HPSC可能从BM迁移到肝脏。此外，与WT小鼠相比，乙醇喂养的Opn−/−小鼠显示出显著的肝脏PMN浸润和含铁血黄素。因此，与WT小鼠相比，乙醇喂养导致Opn−/−小鼠的肝损伤更大。结论：Opn缺失可促进HPSC动员、PMN浸润和肝脏铁沉积，从而加重ALD的严重程度。OPN对HPSC动员到肝脏的年龄相关贡献，PMN的患病率和肝铁的积累，这增强了氧化应激，揭示了新的信号传导机制，可以靶向ALD患者的治疗获益。（Hepatology Communications 2018;2：84-98）
The aim of this study was to investigate the role of osteopontin (OPN) in hematopoietic stem cell (HPSC) mobilization to the liver and its contribution to alcoholic liver disease (ALD). We analyzed young (14‐16 weeks) and old (>1.5 years) wild‐type (WT) littermates and global Opn knockout (Opn−/−) mice for HPSC mobilization to the liver. In addition, WT and Opn−/− mice were chronically fed the Lieber–DeCarli diet for 7 weeks. Bone marrow (BM), blood, spleen, and liver were analyzed by flow cytometry for HPSC progenitors and polymorphonuclear neutrophils (PMNs). Chemokines, growth factors, and cytokines were measured in serum and liver. Prussian blue staining for iron deposits and naphthol AS‐D chloroacetate esterase staining for PMNs were performed on liver sections. Hematopoietic progenitors were lower in liver and BM of young compared to old Opn−/− mice. Granulocyte colony‐stimulating factor and macrophage colony‐stimulating factor were increased in Opn−/− mice, suggesting potential migration of HPSCs from the BM to the liver. Furthermore, ethanol‐fed Opn−/− mice showed significant hepatic PMN infiltration and hemosiderin compared to WT mice. As a result, ethanol feeding caused greater liver injury in Opn−/− compared to WT mice. Conclusion: Opn deletion promotes HPSC mobilization, PMN infiltration, and iron deposits in the liver and thereby enhances the severity of ALD. The age‐associated contribution of OPN to HPSC mobilization to the liver, the prevalence of PMNs, and accumulation of hepatic iron, which potentiates oxidant stress, reveal novel signaling mechanisms that could be targeted for therapeutic benefit in patients with ALD. (Hepatology Communications 2018;2:84–98)
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影响因子：
13.5
作者：
Ge, Xiaodong;Leung, Tung-Ming;Arriazu, Elena;Lu, Yongke;Urtasun, Raquel;Christensen, Brian;Fiel, Maria Isabel;Mochida, Satoshi;Sorensen, Esben S.;Nieto, Natalia
通讯作者：
Nieto, Natalia
DOI：
10.1152/ajpgi.00014.2013
发表时间：
2013-05-01
影响因子：
4.5
作者：
Ge, Xiaodong;Lu, Yongke;Nieto, Natalia
通讯作者：
Nieto, Natalia
通过减轻氧休克来增强造血干细胞移植功效。
影响因子：
64.5
作者：
Mantel CR;O'Leary HA;Chitteti BR;Huang X;Cooper S;Hangoc G;Brustovetsky N;Srour EF;Lee MR;Messina-Graham S;Haas DM;Falah N;Kapur R;Pelus LM;Bardeesy N;Fitamant J;Ivan M;Kim KS;Broxmeyer HE
通讯作者：
Broxmeyer HE
影响因子：
24.5
作者：
Arriazu E;Ge X;Leung TM;Magdaleno F;Lopategi A;Lu Y;Kitamura N;Urtasun R;Theise N;Antoine DJ;Nieto N
通讯作者：
Nieto N
影响因子：
20.3
作者：
Boyerinas, Benjamin;Zafrir, Maya;Sipkins, Dorothy A.
通讯作者：
Sipkins, Dorothy A.